Various conditions caused by diseased or otherwise damaged or functionally impaired organs may be treated by organ transplantations. In particular, transplantation of heart, kidneys, liver, lungs, pancreas, intestine, and thymus can routinely be performed with a reasonable rate of success. A major drawback in organ transplantation however remains the need to find a compatible donor for each recipient patient, since incompatibility between the donor and recipient may result in rejection of the transplanted organ. Transplant rejection can be reduced through serotyping to determine the most appropriate donor-recipient match and through the use of immunosuppressant drugs, although the suitability of these approaches may be diminished due to the medical urgency in some cases. Also, life-long use of immunosuppressant drugs places a burden on the recipient patient in terms of side effects and compliance.
In recent years, cell therapy using various sources of cells is increasingly used for regenerative medicine in humans. Transplantation of cells may provide a valuable alternative or additional (adjunctive) therapy to organ transplantations. Moreover, as not all organs can be effectively transplanted, cell transplantation may frequently be the only cure available. Advantageously, in cell transplantation compatibility related complications may at least in theory become less of a problem. For example, the cells to be transplanted can sometimes be isolated or derived from the patient himself (i.e. autologous cell transplantation), thereby reducing the risk of rejection. Alternatively, allogeneic or even xenogeneic transplant cells may be readily typed and stored for a prolonged time in cell banks or inventories, from which genetically matching or at least compatible cells may be obtained for most recipients.
Where administration of cells to a patient is contemplated, it may be preferable that the cells or cell cultures are selected such as to maximise the tissue compatibility between the patient and the administered cells, thereby reducing the chance of rejection of the administered cells by patient's immune system (graft vs. host rejection). For example, advantageously the cells may be typically selected which have either identical HLA haplotypes (including one or preferably more HLA-A, HLA-B, HLA-C, HLA-D, HLA-DR, HLA-DP and HLA-DQ; preferably one or preferably all HLA-A, HLA-B and HLA-C) to the patient, or which have the most HLA antigen alleles common to the patient and none or the least of HLA antigens to which the patient contains pre-existing anti-HLA antibodies.
Tissue regeneration procedures by means of cell transplantation may be executed using a large variety of cell sources, and commonly using cells having proliferative capacity. For instance, in various human inborn metabolic diseases liver cell transplantation can restore at least some degree of metabolic control. In another example, intraportal transplantation of pancreatic islets offers improved glycaemic control and insulin independence in type 1 diabetes mellitus. For example, pluripotent stem cells capable of differentiating into a plethora of cell lineages, or progenitor cells committed to one or a few cell lineages (multipotent) and displaying varying degrees of differentiation may be used as a cell source for cell transplantation.
Despite some clinical success, current cell transplantation therapies are in need of further improvements. One concern among clinicians and health authorities are the potential consequences of procoagulant activity of certain transplanted cells on engraftment of the cells and other complications. For example, procoagulant activity of islet transplants has been reported to cause graft loss and intraportal thrombotic events (Beuneu et al. Diabetes, 2004, vol. 53, 1407-11; Moberg et al. Lancet, 2002, vol. 360, 2039-45). Procoagulant activity has been also observed in isolated primary hepatocytes (Stéphenne et al. Liver Transpl., 2007, vol. 13, 599-606).
Consequently, there persists an urgent need in the art to improve cell transplantation success and cell engraftment potential, and in particular to reduce prothrombotic complications associated with cell transplantation.
Furlani et al. Microvasc Res., 2009, vol. 77, 370-6 studied the kinetics of human mesenchymal stem cells after intravascular administration into SCID mouse cremaster vasculature by intra-vital microscopy. The authors proposed that intra-arterial mesenchymal stem cells infusion may lead to occlusion in the distal vasculature due to the cells' relatively large size.